Eagleton was born in St. Louis, Missouri, the son of Zitta Louise (Swanson) and Mark David Eagleton, a politician who had run for mayor. His paternal grandparents were Irish immigrants, and his mother had Swedish, Irish, French, and Austrian ancestry.[1]

Eagleton married Barbara Ann Smith of St. Louis on January 26, 1956. A son, Terence, was born in 1959, and a daughter, Christin, was born in 1963.

He was elected circuit attorney of the City of St. Louis in 1956. During his tenure, he appeared on the TV show What's My Line? (episode #355) as "District Attorney of St. Louis". (He stumped the panel.)[3] He was elected Missouri Attorney General in 1960, at the age of 31 (the youngest in the state's history). He was elected the 38th Lieutenant Governor of Missouri in 1964, and won a U.S. Senate seat in 1968 unseating incumbent Edward V. Long in the Democratic primary and narrowly defeating Congressman Thomas B. Curtis in the general election.

Between 1960 and 1966, Eagleton checked himself into the hospital three times for physical and nervous exhaustion, receiving electroconvulsive therapy twice.[4] He was also known to have suffered from depression.

The hospitalizations, which were not widely publicized, had little effect on his political aspirations, although the St. Louis Post-Dispatch was to note, in 1972, immediately after his vice presidential nomination: "He had been troubled with gastric disturbances, which led to occasional hospitalizations. The stomach troubles have contributed to rumors that he had a drinking problem."[4]

On April 25, 1972, George McGovern won the Massachusetts primary, and conservative journalist Robert Novak phoned Democratic politicians around the country. On April 27, 1972 Novak reported in a column his conversation with an unnamed Democratic senator about McGovern.[5][6]

Novak quoted the senator as saying "The people don't know McGovern is for amnesty, abortion, and legalization of pot. Once middle America — Catholic middle America, in particular — finds this out, he’s dead."[5] Because of the column McGovern became known as the candidate of "amnesty, abortion, and acid."[7][8]

On July 15, 2007, several months after Eagleton's death, Novak said on Meet the Press that the unnamed senator was Eagleton.[8] Novak was accused in 1972 of manufacturing the quote, but stated that to rebut the criticism, he took Eagleton to lunch after the campaign and asked whether he could identify him as the source; the senator refused.[5] "Oh, he had to run for re-election", said Novak, "the McGovernites would kill him if they knew he had said that."[8] Political analyst Bob Shrum says that Eagleton would never have been selected as McGovern's running mate if it had been known at the time that Eagleton was the source of the quote.[8] "Boy, do I wish he would have let you publish his name. Then he never would have been picked as vice president," said Shrum.[8] "Because the two things, the two things that happened to George McGovern — two of the things that happened to him — were the label you put on him, number one, and number two, the Eagleton disaster. We had a messy convention, but he could have, I think in the end, carried eight or 10 states, remained politically viable. And Eagleton was one of the great train wrecks of all time."[8]

In 1972, Richard Nixon appeared unbeatable. When McGovern won the Democratic nomination for President, virtually all of the high-profile Democrats, including Ted Kennedy, Walter Mondale, Hubert Humphrey, Edmund Muskie,[9] and Birch Bayh, turned down offers to run on the ticket. McGovern had been convinced that Kennedy would join the ticket. Kennedy ended up refusing. McGovern campaign manager Gary Hart suggested BostonMayorKevin White. McGovern called White, and received "an emphatic yes", but the leader of the Massachusetts delegation, Ken Galbraith, said the Massachusetts delegation would walk-out if the announcement was made to the Convention that McGovern had chosen White as his vice-presidential candidate, as White had backed Muskie during the Massachusetts primary (yet, Massachusetts ended up being the only state that McGovern would carry in Electoral College votes on November 7, Election Day).

McGovern then asked Senator Gaylord Nelson to be his running mate. Nelson declined but suggested Tom Eagleton, whom McGovern ultimately chose, with only a minimal background check. Eagleton made no mention of his earlier hospitalizations, and in fact decided with his wife to keep them secret from McGovern while he was flying to his first meeting with the Presidential nominee.

McGovern said he would back Eagleton "1000 percent". Subsequently, McGovern consulted confidentially with preeminent psychiatrists, including Eagleton's own doctors, who advised him that a recurrence of Eagleton's depression was possible and could endanger the country should Eagleton become president.[10][11][12][13][14] On August 1, Eagleton withdrew at McGovern's request and, after a new search by McGovern, was replaced by Kennedy in-lawSargent Shriver.[15]

A Time magazine poll taken at the time found that 77 percent of the respondents said "Eagleton's medical record would not affect their vote." Nonetheless, the press made frequent references to his 'shock therapy', and McGovern feared that this would detract from his campaign platform.[16]

McGovern's handling of the controversy was an opening for the Republican campaign to raise serious questions about his judgment. In the general election, the Democratic ticket won only Massachusetts and the District of Columbia.

Missouri returned Eagleton to the Senate in 1974; he won 60% of the popular vote against Thomas B. Curtis, who had been his opponent in 1968. In 1980, he was re-elected by a closer-than-expected margin over St. Louis County Executive Gene McNary.

During the 1980 election, Eagleton's niece Elizabeth Eagleton Weigand and lawyer Stephen Poludniak were arrested for blackmail after they threatened to spread false accusations that Eagleton was bisexual. Eagleton told reporters that the extorted money was to be turned over to the Church of Scientology. Poludniak and Weigand appealed the conviction all the way to the U.S. Supreme Court, arguing that they could not have gotten a fair trial because of "the massive publicity surrounding this case, coupled with the pre-existing sentiment in favor of Sen. Eagleton". The Court turned down the appeal.

Eagleton was one of the authors of The Hatch-Eagleton Amendment, introduced in the Senate on January 26, 1983 with Sen. Orrin Hatch (R), which stated that "A right to abortion is not secured by this Constitution".

Eagleton led a group, Catholics for Amendment 2, composed of prominent Catholics that challenged church leaders' opposition to embryonic stem cell research and to a proposed state constitutional amendment that would have protected such research in Missouri. The group e-mailed a letter to fellow Catholics explaining reasons for supporting Amendment 2.[19] The amendment ensures that any federally approved stem cell research and treatments would be available in Missouri. "[T]he letter from Catholics for Amendment 2 said the group felt a moral obligation to respond to what it called misinformation, scare tactics and distortions being spread by opponents of the initiative, including the church."[19]

During the 2000s, Eagleton served on the Council of Elders for the George and Eleanor McGovern Center for Leadership and Public Service at Dakota Wesleyan University.[20]

On July 23, 1996, Eagleton delivered a warm introductory speech for George McGovern during a promotional tour for McGovern's book, Terry: My Daughter's Life-and-Death Struggle with Alcoholism, at The Library, Ltd., in St. Louis, Missouri. At that time, McGovern spoke favorably about Eagleton and reminisced about their short-lived presidential ticket in 1972.[21]

Eagleton died in St. Louis on March 4, 2007, of heart and respiratory complications. Eagleton donated his body to medical science at Washington University.[22] He wrote a farewell letter to his family and friends months before he died, citing that his dying wishes were for people to "go forth in love and peace — be kind to dogs — and vote Democratic".[23]